Discovery and Early Clinical Development of Selective Immunoproteasome Inhibitors.
Discovery and Early Clinical Development of Selective Immunoproteasome Inhibitors.
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作者：
Kirk CJ;Muchamuel T;Wang J;Fan RA
20 S蛋白酶体蛋白水解活性的抑制剂已经改变了多种B细胞恶性肿瘤的治疗。这些药剂也已成功用于治疗患有自身免疫性疾病和免疫介导的病症的患者。然而，需要新的药物来充分释放蛋白酶体抑制剂作为免疫调节药物的潜力。免疫蛋白酶体的选择性抑制剂在临床前模型中具有广泛的抗炎活性的发现已经导致多种化合物进入临床试验。本文综述了免疫蛋白酶体抑制剂的抗炎潜力和KZR-616的早期发展，KZR-616是第一个进入临床试验的免疫蛋白酶体选择性抑制剂。
Inhibitors of the proteolytic activity of the 20S proteasome have transformed the treatment of multiple B-cell malignancies. These agents have also been employed with success in the treatment of patients with autoimmune diseases and immune-mediated disorders. However, new agents are needed to fully unlock the potential of proteasome inhibitors as immunomodulatory drugs. The discovery that selective inhibitors of the immunoproteasome possess broad anti-inflammatory activity in preclinical models has led to the progression of multiple compounds to clinical trials. This review focuses on the anti-inflammatory potential of immunoproteasome inhibition and the early development of KZR-616, the first selective inhibitor of the immunoproteasome to reach clinical testing.
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6
作者：
Huber EM;Groll M
通讯作者：
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Kisselev AF
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64.5
作者：
KING, RW;PETERS, JM;KIRSCHNER, MW
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KIRSCHNER, MW